This invention relates to inhibitors of thrombin which are useful in the prevention of clot formation in warm blooded mammals. In particular, it relates to N-phenylalanyl and N-phenylglyclyl derivatives of the dipeptide of L-azetidine-2-carboxylic acid and L-arginine aldehyde and to derivatives and salts thereof.
Thrombin inhibition is currently treated by the administration of heparins and coumarins e.g. warfarin. The mechanism by which these agents act has been the subject of extensive study. Heparins are administered parenterally and levels of the drug must be carefully monitored to control unwanted bleeding in the patient. Coumarins act by blocking or inhibiting the formation of prothrombin and generally require some time to achieve effectiveness. One regime of treatment e.g. of phlebitis utilizes heparin initially followed by coumarin. Although both of these agents are effective, there remains a need for thrombin inhibitors which act quickly to prevent clot formation and which do not interfere with the action of plasmin in the dissolution of existing clots or with administered clot lysing agents such as tissue plasminogen activators.